Long-Term Protection against Diphtheria in the Netherlands after 50 Years of Vaccination: Results from a Seroepidemiological Study

Abstract

Background and aims: To evaluate the National Immunisation Programme (NIP) a population-based cross-sectional seroepidemiological study was performed in the Netherlands. We assessed diphtheria antitoxin levels in the general Dutch population and in low vaccination coverage (LVC) areas where a relatively high proportion of orthodox Protestants live who decline vaccination based on religious grounds. Results were compared with a nationwide seroepidemiological study performed 11 years earlier.

Methods: In 2006/2007 a national serum bank was established. Blood samples were tested for diphtheria antitoxin IgG concentrations using a multiplex immunoassay for 6383 participants from the national sample (NS) and 1518 participants from LVC municipalities. A cut-off above 0.01 international units per ml (IU/ml) was used as minimum protective level.

Results: In the NS 91% of the population had antibody levels above 0.01 IU/ml compared to 88% in the 1995/1996 serosurvey (p<0.05). On average, 82% (vs. 78% in the 1995/1996 serosurvey, p<0.05) of individuals from the NS born before introduction of diphtheria vaccination in the NIP and 46% (vs. 37% in the 1995/1996 serosurvey, p = 0.11) of orthodox Protestants living in LVC areas had antibody levels above 0.01 IU/ml. Linear regression analysis among fully immunized individuals (six vaccinations) without evidence of revaccination indicated a continuous decline in antibodies in both serosurveys, but geometric mean antibodies remained well above 0.01 IU/ml in all age groups.

Conclusions: The NIP provides long-term protection against diphtheria, although antibody levels decline after vaccination. As a result of natural waning immunity, a substantial proportion of individuals born before introduction of diphtheria vaccination in the NIP lack adequate levels of diphtheria antibodies. Susceptibility due to lack of vaccination is highest among strictly orthodox Protestants. The potential risk of spread of diphtheria within the geographically clustered orthodox Protestant community after introduction in the Netherlands has not disappeared, despite national long-term high vaccination coverage.

Fig 1. Weighted age-specific geometric mean IgG concentrations of diphtheria antibody in the national sample of the 1995/1996 serosurvey (n = 7691) and 2006/2007 serosurvey (n = 6383).

The error bars represent the 95% confidence intervals. Year of birth indicates median year of birth corresponding to the defined age category. The dashed horizontal line represents the minimum level of protection of 0.01 IU/ml. The textbox shows changes in the National Immunization Program.

Fig 2. Weighted age-specific seroprevalences (%) of diphtheria antibody in the national sample of the 1995/1996 serosurvey (n = 7691) (Fig 2a) and in the national sample of the 2006/2007 serosurvey (n = 6383) (Fig 2b).

Fig 3. Persistence of diphtheria IgG antibody in 10 to 34 and 10 to 39 year old individuals, in the national sample of the 1995/1996 serosurvey (n = 961) and 2006/2007 serosurvey (n = 971), who were completely immunized against diphtheria according to the NIP, without evidence of revaccination.